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Open Access Original research

Pretargeted immuno-PET of CEA-expressing intraperitoneal human colonic tumor xenografts: a new sensitive detection method

Rafke Schoffelen1*, Winette TA van der Graaf2, Robert M Sharkey3, Gerben M Franssen1, William J McBride4, Chien-Hsing Chang5, Peter Laverman1, David M Goldenberg3, Wim JG Oyen1 and Otto C Boerman1

Author Affiliations

1 Dept. of Nuclear Medicine, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, 9101, The Netherlands

2 Dept. of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, 6500 HB, Nijmegen, 9101, The Netherlands

3 Garden State Cancer Center, Belleville, NJ, 07109, USA

4 Immunomedics, Inc., Morris Plains, NJ, 07950, USA

5 IBC Pharmaceuticals, Immunomedics, Inc., Morris Plains, NJ, 07950, USA

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EJNMMI Research 2012, 2:5  doi:10.1186/2191-219X-2-5

Published: 27 January 2012

Abstract

Background

In this study, pretargeted immuno-positron-emission tomography [PET] with a bispecific monoclonal anti-carcinoembryonic antigen [CEA] (CEACAM5) × anti-hapten antibody (bispecific monoclonal antibody [bsmAb]) and a small (1.5 kD) peptide labeled with 68Ga was compared to fludeoxyglucose [18F-FDG]-PET for detecting intraperitoneal [i.p.] CEA-expressing human colonic tumor xenografts in nude mice.

Methods

Two groups of female BALB/c nude mice were inoculated with LS174T human colonic tumor cells i.p. One group received 5 MBq 18F-FDG, and the other received intravenous injections of the bsmAb, followed 16 h later with 5 MBq of 68Ga-labeled peptide. One hour after the radiolabeled peptide or FDG was given, micro-PET/computed tomography images were acquired. Thereafter, the uptake of the 68Ga or 18F in dissected tissue was determined.

Results

Within 1 h, high uptake of the 68Ga-labeled peptide in the tumor lesions (23.4 ± 7.2% ID/g) and low background activity levels were observed (e.g., tumor-to-intestine ratio, 58 ± 22). This resulted in a clear visualization of all intra-abdominal tumor lesions ≥ 10 μL and even some tumors as small as 5 μL (2 mm diameter). 18F-FDG efficiently localized in the tumors (8.7 ± 3.1% ID/g) but also showed physiological uptake in various normal tissues (e.g., tumor-to-intestine ratio, 3.9 ± 1.1).

Conclusions

Pretargeted immuno-PET with bsmAb and a 68Ga-labeled peptide could be a very sensitive imaging method for imaging colonic cancer, disclosing occult lesions.

Keywords:
colorectal cancer; carcinoembryonic antigen; imaging; PET; pretargeting; bispecific antibodies